Li Wei

CONTEXT: In 2020, the terminology of metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). OBJECTIVES: This work aimed to investigate the prevalence and incidence of MAFLD and evaluate its effects on incident extrahepatic diseases. METHODS: A total of 6873 individuals, with a 4.6-year follow-up, were included in this study. Associations of MAFLD and NAFLD with diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) were examined using logistic regression and Cox proportional hazards models. RESULTS: The prevalence of NAFLD and MAFLD was 40.3% (95% CI, 39.2%-41.5%) and 46.7% (95% CI, 45.6%-47.9%), respectively. Additionally, 321 (4.7%) and 156 (2.3%) participants had MAFLD with excessive alcohol consumption and hepatitis B virus (HBV) infection. During the follow-up period, the incidence of NAFLD and MAFLD was 22.7% (95% CI, 21.3%-24.0%) and 27.0% (95% CI, 25.5%-28.4%). MAFLD was associated with higher risks of incident diabetes (risk ratio [RR] 2.08; 95% CI, 1.72-2.52), CKD (RR 1.64; 95% CI, 1.39-1.94), and CVD (hazard ratio 1.44; 95% CI, 1.15-1.81). Similar associations for NAFLD were observed. Furthermore, the MAFLD subgroups with excessive alcohol consumption (RR 2.49; 95% CI, 1.64-3.78) and HBV infection (RR 1.98; 95% CI, 1.11-3.52) were associated with higher risks of incident diabetes. CONCLUSION: The change from NAFLD to MAFLD did not greatly affect the associations with diabetes, CKD, and CVD. MAFLD further identified those patients of metabolically fatty liver combined with excessive alcohol consumption and HBV infection, who had increased risks of incident diabetes compared with those of non-fatty liver.

Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK) pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC) phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1) inhibition of AMPK activity by Compound C, (2) suppression of AMPKα expression by siRNA, and (3) blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.

BACKGROUND: Previous studies have documented that visceral adipose tissue is positively associated with the risk of diabetes. However, the association of subcutaneous adipose tissue with diabetes risk is still in dispute. We aimed to assess the associations between different adipose distributions and the risk of newly diagnosed diabetes in Chinese adults. METHODS: The Shanghai Nicheng Cohort Study was conducted among Chinese adults aged 45-70 years. The baseline data of 12,137 participants were analyzed. Subcutaneous and visceral fat area (SFA and VFA) were measured by magnetic resonance imaging. Diabetes was newly diagnosed using a 75 g oral glucose tolerance test. RESULTS: The multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) of newly diagnosed diabetes per 1-standard deviation increase in SFA and VFA were 1.29 (1.19-1.39) and 1.61 (1.49-1.74) in men, and 1.10 (1.03-1.18) and 1.56 (1.45-1.67) in women, respectively. However, the association between SFA and newly diagnosed diabetes disappeared in men and was reversed in women (OR 0.86 [95% CI, 0.78-0.94]) after additional adjustment for body mass index (BMI) and VFA. The positive association between VFA and newly diagnosed diabetes remained significant in both sexes after further adjustment for BMI and SFA. Areas under the receiver operating characteristic curve of newly diagnosed diabetes predicted by VFA (0.679 [95% CI, 0.659-0.699] for men and 0.707 [95% CI, 0.690-0.723] for women) were significantly larger than by the other adiposity indicators. CONCLUSIONS: SFA was beneficial for lower risk of newly diagnosed diabetes in women but was not associated with newly diagnosed diabetes in men after taking general obesity and visceral obesity into account. VFA, however, was associated with likelihood of newly diagnosed diabetes in both Chinese men and women.